Novel crystalline forms of 4-[4-[4-(hydroxydiphenylmethyl)-1- piperidinyl]-1-hydroxybutyl]-$g(a)-dimethylbenzene acetic acid and its hydrochloride

ABSTRACT

The present invention is related to novel polymorph of Fexofenadine and Fexofenadine hydrochloride of formula 1 and process of preparation thereof. The present invention is also directed to provide pure novel polymorphs of Fexofenadine and its hydrochloride by a simple process which is cost effective, commercially viable and environment friendly.

FIELD OF THE INVENTION

[0001] The present invention relates to a novel crystalline form offexofenadine hydrochloride and to a process for the preparation thereof.More specifically, the present invention relates to a novel anhydrouscrystalline Form X of fexofenadine hydrochloride. The present inventionalso relates to a novel crystalline form of fexofenadine, particularlyForm A of fexofenadine and to a process for the preparation thereof.

BACKGROUND OF INVENTION

[0002] Chemically fexofenadine hydrochloride is4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzeneacetic acid hydrochloride. It is also known as terfenadine carboxylicacid metabolite. It is represented by Formula 1.

[0003] Fexofenadine hydrochloride is useful as an antihistamine, anddoes not cause the adverse effects associated with the administration ofterfenadine including abnormal heart rhythms in some patients with liverdisease or patients who also take the antifimgal drug ketoconazole orthe antibiotic erythromycin.

[0004] U.S. Pat. No. 4,254,129 (“the '129 patent”) entitled PiperidineDerivatives issued on Mar. 3, 1981. The '129 patent relates tosubstituted piperidine derivatives and methods of making and using them.The disclosed compounds, including fexofenadine and its pharmaceuticallyacceptable salts and individual optical isomers, are purported to beuseful as antihistamines, antiallergy agents and bronchodilators.

[0005] The '129 patent discloses a process for the preparation offexofenadine having a melting point of 195-197° C. The recrystallizationprocess exemplified therein in Example 3, column 13, involves use of amixture of solvents for preparation of fexofenadine.

[0006] WO 95/31437 discloses processes for preparing hydrated andanhydrous forms of piperidine derivatives, polymorphs and pseudomorphsthereof, which are useful as antihistamines, antiallergic agents andbronchodilators.

[0007] WO 95/31437 discloses the preparation of anhydrous forms offexofenadine hydrochloride by subjecting the hydrated fexofenadinehydrochloride to an azeotropic distillation or to water minimizingrecrystallization. In the invention described in this application,unlike the process described in WO 95/31437, hydrated FexofenadineHydrochloride is not converted to anhydrous Fexofenadine Hydrochloride,but instead Fexofenadine is converted to Form A of Fexofenadine and thento anhydrous Form X of Fexofenadine Hydrochloride. The novel anhydrouscrystalline form of Fexofenadine Hydrochloride is obtained according tothe present invention directly from the novel precursor i.e.Fexofenadine without generating a hydrated form. The starting materialused Fexofenadine (Base) is different than described in WO 95/31437.

[0008] WO 00/71124A1 discloses amorphous fexofenadine hydrochlorideprocess, its preparation and a composition containing it.

[0009] Fexofenadine obtained in the prior art processes, is a mixture ofregioisomers of fexofenadine containing 33% of para isomer and 67% ofmeta isomer. These components are referred to as inseparable and it isalso stated that it is not possible to obtain either of the regioisomersin substantially pure form. On the other hand, Fexofenadine preparedaccording to the process of this invention has a purity of >99.5%. Inthe novel crystalline Fexofenadine of this invention, the meta isomer ofFexofenadine is at a level of below 0.1%. Purity of fexofenadine iscritical when it is used for the conversion to its hydrochloride saltsince it is very difficult to remove any undesired impurities, includingregioisomers, from the desired compound in last late processing stage.Removing the impurities increases the cost of production. Hence it isgenerally preferred that the HPLC purity of fexofenadine is greater than99.5%.

[0010] Another beneficial aspect of the present invention is that, thefexofenadine hydrochloride is obtained in almost quantitative yield fromthe precursor i.e. fexofenadine. Almost quantitative yield means thatthe pure fexofenadine is converted to fexofenadine hydrochloridequantitatively (>92% yield of theory), with almost no yield loss, as thefexofenadine base itself is >99.5% pure as compared to fexofenadineprepared by the prior art processes.

SUMMARY OF THE INVENTION

[0011] Therefore, an object of the present invention is to provide anovel crystalline form of fexofenadine and a process for itspreparation.

[0012] Another object of the present invention is to provide a novelanhydrous crystalline form of fexofenadine hydrochloride (Formula 1) anda process for its preparation, which can be obtained directly fromfexofenadine without generating a hydrated form of fexofenadinehydrochloride.

[0013] A further object of the present invention is to provide purenovel polymorphs of fexofenadine and its hydrochloride by a simpleprocess which is cost effective, commercially viable and environmentallyfriendly.

BRIEF DESCRIPTION OF ACCOMPANYING DRAWINGS

[0014]FIG. 1 is a characteristic X-ray powder diffraction pattern ofForm A of fexofenadine. Vertical axis: Intensity (CPS); Horizontal axis:Two Theta (degrees). The significant d values (A°) obtained are 23.11,11.50, 8.29, 7.03, 6.67, 6.16, 6.02, 5.75, 5.43, 5.33, 5.07, 4.69, 4.63,4.44, 4.20, 4.15, 4.07, 3.55, and 3.44.

[0015]FIG. 2 is a characteristic infrared absorption spectrum inpotassium bromide of aforementioned Form A of fexofenadine. [Verticalaxis, Tramission (%); Horizontal axis: Wave number (cm⁻¹)]. Thecharacteristic peaks for Form A are indicated at 3421, 3058, 2936, 2366,2343, 1571, 1509, 1490, 1447, 1390, 1334, 1167, 1097, 1073, 1018, 960,916, 849, 745, 706, 666, 637, 617, 541.

[0016]FIG. 3 is a characteristic of differential scanning calorimetrythermogram of aforesaid Form A of Fexofenadine. Vertical axis: mW;Horizontal axis: Temperature (° C.). The DSC thermogram exhibits a meltendotherm at about 230.38° C.

[0017]FIG. 4 is a characteristic X-ray powder diffraction pattern ofForm X of fexofenadine hydrochloride. Vertical axis: Intensity (CPS);Horizontal axis: Two Theta (degrees). The significant d values (A°)obtained are 16.05, 12.98, 8.29, 8.06, 6.25, 5.97, 5.54, 5.41, 4.89,4.70, 4.55, 4.37, 4.32, 4.15, 4.03, 3.80, 3.67, 3.57, 3.42.

[0018]FIG. 5 is a characteristic infrared absorption spectrum inpotassium bromide of aforementioned Form X of Fexofenadinehydrochloride. [Vertical axis, Tramission (%); Horizontal axis: Wavenumber (cm⁻¹)]. The characteristic peaks for Form X are indicated at3370, 2965, 2652, 1717, 1472, 1448, 1250, 1158, 1100, 1068, 995, 962,840, 747, 703, 638, 560.

[0019]FIG. 6 is a characteristic of differential scanning calorimetrythermogram of aforesaid Form X of Fexofenadine hydrochloride. Verticalaxis: mW; Horizontal axis: Temperature (° C.). The DSC thermogramexhibits a melt endotherm at about 186.56° C.

DETAILED DESCRIPTION OF INVENTION

[0020] The present invention provides a novel crystalline form ofFexofenadine, which is designated as Form A for convenience. The processfor the preparation of novel crystalline Form A, comprisesrecrystallization of crude fexofenadine in an alcohol followed byazeotropically refluxing Fexofenadine in a non polar organic solvent,organic solvent or a mixture thereof and the subsequent isolation of thedesired Form A.

[0021] Form A is prepared by a process, which comprises:

[0022] a. recrystallizing crude Fexofenadine in a (C₁-C₃)alkanolfollowed by;

[0023] b. azeotropically refluxing Fexofenadine in a non polar organicsolvent, an organic solvent or a mixture thereof for 15 minutes to 6hours, preferably 1-3 hours;

[0024] c. stirring the reaction mixture at ambient temperature for 30minutes to 2 hours; and

[0025] d. isolating the Form A of Fexofenadine by conventional methods.

[0026] Crude fexofenadine can be recrystallized in methanol, ethanol orisopropanol, preferably methanol. The ratio of crude Fexofenadine to the(C₁-C₃) alkanol is 1:10-20. The ratio of fexofenadine to nonpolarorganic solvent and/or organic solvent in step b) is 1:10-15.

[0027] The non polar organic solvents referred to herein are selectedfrom xylene or toluene or a (C₆-C₉) alkyl such as n-hexane, hexane,heptane, octane, nonane or cyclohexane. Toluene is the preferred nonpolar organic solvent. The organic solvents are (C₁ to C₄) alkylacetates and are selected from methyl, ethyl, propyl, and butyl acetate,preferably ethyl acetate.

[0028] The Form A of Fexofenadine can be identified by the followingcharacteristics:

[0029] a visual melting point (capillary tube) in the range of about218-228° C.;

[0030] a melting endotherm at about 227-231° C. as determined bydifferential scanning calorimetry;

[0031] and an X-ray powder diffraction pattern essentially as shown inthe Table 1. TABLE 1 D-Space, Intensity, I/I_(o), Angstroms % d valueI/Io 23.11 51 11.50 44 8.29 79 7.03 28 6.67 48 6.16 50 6.02 24 5.75 235.43 75 5.33 52 5.07 100 4.69 27 4.63 32 4.44 66 4.20 52 4.15 55 4.07 383.55 21 3.44 20

[0032] According to another aspect, the present invention provides aprocess for preparing a novel crystalline form of FexofenadineHydrochloride, designated as Form X.

[0033] The process for the preparation of novel crystalline Form X offexofenadine hydrochloride, comprises reaction of fexofenadine Form A innon polar solvent, with a suitable solvent containing hydrogen chlorideand isolating the desired Form X of fexofenadine hydrochloride which canbe obtained directly from fexofenadine without generating a hydratedform of fexofenadine hydrochloride.

[0034] The Form X polymorph is prepared by a process, which comprises:

[0035] a. recrystallizing crude Fexofenadine in (C₁-C₃)alkanol followedby,

[0036] b. azeotropically refluxing Fexofenadine in a non polar organicsolvent, an organic solvent or mixtures thereof for 15 minutes to 6hours, preferably 1-3 hours;

[0037] c. stirring the reaction mixture at ambient temperature for 30min to 2 hours;

[0038] d. optionally isolating the Fexofenadine Form A by conventionalmethods;

[0039] e. if isolated, suspending Fexofenadine Form A, in a non polarorganic solvent;

[0040] f. adjusting the pH of the reaction mass to 1 to 3, preferably 2with a suitable solvent containing hydrogen chloride;

[0041] g. stirring the reaction mass for 30 minutes to 18 hours,preferably 1-10 hours and more preferably 3-6 hours at ambienttemperature;

[0042] h. filtering the solid obtained followed by drying at 60-100° C.;

[0043] i. suspending the solid obtained in step (h) in an alkyl acetateand heating the reaction mixture to reflux for 0.5-6 hours preferably1-3 hours;

[0044] j. stirring the reaction mixture at ambient temperature for 20minutes to 2 hours; and

[0045] k. isolating the anhydrous crystalline Form X of4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzeneacetic acid hydrochloride, by conventional methods.

[0046] The preparation of Form X can be accomplished without isolationof Form A. The preparation of Form X can proceed directly from step (c)to step (f) eliminating steps (d) and (e).

[0047] In variation of above process the preparation of novel Form Xpolymorph may be accomplished by drying the solid obtained in step (h)at 110-160° C. under reduced pressure for 30 minutes to 10 hours,preferably 2-5 hours.

[0048] The ratio of solid to alkyl acetate in step (i) is 1:10-15.

[0049] Yet another aspect of the present invention is to provide aprocess for preparing a novel crystalline form of FexofenadineHydrochloride, designated as Form X, by seeding technique.

[0050] This process comprises:

[0051] a. recrystallizing crude Fexofenadine in a (C₁-C₃)alkanolfollowed by;

[0052] b. azeotropically refluxing Fexofenadine in a non polar organicsolvent for 3-4 hours;

[0053] c. optionally isolating the Fexofenadine Form A obtained in stepb) by conventional methods accompanied by drying at below 100° C.;

[0054] d. suspending the Fexofenadine Form A obtained in step c) oradding to the mixture of step b) a mixture of a nonpolar organicsolvents selected from toluene or xylene or a (C₆-C₉)alkyl; or anorganic solvent selected from (C₁-C₄) alkyl acetate preferably ethylacetate; and isopropanol, the ratio of solvent to isopropanol being7-9:3-1 preferably 9:1;

[0055] e. adjusting the pH of the solution of step d) to 1 to 3preferably 2 with a suitable solvent containing hydrogen chloride;

[0056] f. filtering the solution obtained in step e) to removeparticulate matter;

[0057] g. seeding the solution of step f) with crystals of novelcrystalline Form X and stirring the reaction mass at ambient temperatureto separate the solid;

[0058] h. filtering the solid obtained in step g) followed by washingwith a nonpolar organic solvent, organic solvent or hydrocarbon solvent;and

[0059] i. drying the anhydrous crystalline Form X of4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]α,α-dimethylbenzeneacetic acid hydrochloride at 70-100° C.

[0060] The crude fexofenadine may be recrystallized in a C₁-C₃ alkanolsuch as methanol, ethanol or isopropanol, preferably, methanol.

[0061] The non polar organic solvents referred to herein are selectedfrom xylene or toluene or a (C₆-C₉) alkyl such as n-hexane, hexane,heptane, octane, nonane or cyclohexane. Mixtures of solvents maybe usedthereof Toluene is the preferred solvent. The organic solvents are(C₁-C₄) alkyl acetates and are selected from methyl, ethyl, propyl andbutyl acetate preferably ethyl acetate.

[0062] The suitable solvent containing hydrogen chloride referred toherein is selected from methanol, ethanol, isopropanol or t-butanol,preferably isopropanol.

[0063] The ratio of crude fexofenadine to the C₁-C₃ alkanol is 1:10-20.The ratio of fexofenadine to the solvents in step b. is 1:10-15.

[0064] The hydrocarbon solvent is selected from hexane or cyclohexane,preferably cyclohexane.

[0065] The Form X of Fexofenadine hydrochloride obtained by theprocesses described above can be identified by

[0066] a visual melting point (capillary tube) in the range of about180-188° C.;

[0067] a melting endotherm at about 180-189° C. as determined bydifferential scanning calorimetry;

[0068] and an X-ray powder diffraction pattern essentially as shown inthe Table 2. TABLE 2 D-Space, Intensity, I/I_(o), Angstroms % d valueI/Io 16.05 78 12.98 65 8.29 62 8.06 27 6.25 46 5.97 29 5.54 100 5.41 384.89 69 4.70 97 4.55 92 4.37 23 4.32 33 4.15 22 4.03 58 3.80 43 3.67 343.57 33 3.42 35

[0069] The present invention provides a improved method for thepreparation of Fexofenadine Form A in its pure form by a crystallizationprocess which requires only a single solvent. This solvent may berecovered and reused, thereby rendering the process cost effective andenvironmentally friendly.

[0070] The novel polymorphic forms of fexofenadine of this invention mayif desired be converted into one of its pharmaceutically acceptablesalts.

[0071] It is noteworthy to mention that both Fexofenadine and itshydrochloride obtained by the present invention are pure and well suitedfor formulation. Most pharmaceuticals formulation processes arefaciliated by use of the active materials that are free flowing highmelting solids. The novel anhydrous crystalline Form A and X ofFexofenadine Hydrochloride of the present invention are a high meltingsolid, very suited for formulation.

EXAMPLES

[0072] The present invention is illustrated by the following examples,which are not intended to limit the effective scope of the claims.

Reference Example—for the Preparation of Fexofenadine Crude

[0073] To a solution of a mixture of methyl4-[4-[4-(hydroxydiphenylmethyl)1piperidinyl]-1-oxobutyl]-α,α-dimethylbenzeneacetatehydrochloride and methyl3-[4-[4-(hydroxydiphenylmethyl)1-piperidinyl]-1-oxobutyl]-α,α-dimethylbenzeneacetatehydrochloride (100 g) in methanol (600 ml) is added aqueous sodiumhydroxide (36.4 g sodium hydroxide in 132 ml of water). The mixture isheated to reflux for about 2-4 hours. Completion of the reaction ismonitored by TLC method and upon completion the reaction mixture iscooled to ambient temperature accompanied by addition of sodiumborohydride (6.8 g). The reaction mixture is heated to 50-60° C. andmaintained at the same temperature for about 14 hours (completion of thereaction is monitored by TLC method), and subsequently cooled to ambienttemperature accompanied by carbon treatment. The clear filtrate obtainedafter carbon treatment, is stripped of methanol followed by addition ofwater (300 ml) and acetone (200 ml). The pH of the reaction mixture isthen adjusted to ˜6 with acetic acid, stirred for 5 hours and thenfiltered, followed by water wash (200 ml) to afford crude Fexofenadine.

[0074] Yield: 72 g

Example 1 Preparation of Pure Fexofenadine

[0075] A solution of Fexofenadine crude (500 g; prepared as perreference example) in methanol (4000 ml) is refluxed for 1 hour and thereaction mixture is then cooled to room temperature. The precipitatedpure Fexofenadine obtained was filtered and washed with methanol (250ml). Repeated recrystallization in methanol afforded pure Fexofenadineof desired purity.

[0076] Purity by HPLC 99.85%; Meta isomer<0.1%

Example 2 Step 1 Preparation of Form A from Pure Fexofenadine

[0077] A suspension of pure Fexofenadine (180 g) in toluene (1800 ml) isazeotropically refluxed for 2 and a half hours. The reaction mixture isthen cooled to room temperature and stirred for about 40 minutes. Aftercompletion of this step the reaction mixture was filtered and washedwith toluene (180 ml) and the obtained Form A of Fexofenadine is driedat 80-85° C. under atmospheric pressure till constant weight.

[0078] Yield 179.2 g: M.R (melting range) 220-224° C.

Step 2 Preparation of Form X of Fexofenadine Hydrochloride

[0079] To the Fexofenadine Form A (170 g; prepared as per procedure instep 1), toluene (1700 ml) is added followed by slow addition ofisopropanol hydrogen chloride (prepared by purging hydrogen chloride toisopropyl alcohol) to pH 2. The reaction mass is then stirred for 10hours 15 minutes. The solid obtained is filtered, washed with toluene(170 ml) and dried under vacuum at 75-80° C. Solid thus obtained (140 g)is refluxed in ethyl acetate (2800 ml) for about 1 hour. The reactionmixture is then cooled to room temperature and stirred for 1 hour 30minutes. The reaction mass is filtered and washed with ethyl acetate(140 ml). The desired Form X of Fexofenadine hydrochloride is obtainedafter drying at 78-85° C. under atmospheric pressure till constantweight.

[0080] Yield 129.6 g: M.R 183-187° C.

Example 3 Preparation of Form X of Fexofenadine Hydrochloride

[0081] To the Fexofenadine Form A (95 g; prepared as per procedure underExample 2, step 1), toluene (950 ml) is added followed by slow additionof isopropanol hydrogen chloride (prepared by purging hydrogen chlorideto isopropyl alcohol) to pH 2. The reaction mass is then stirred for 2hours 45 minutes. The reaction mass is filtered and washed with toluene(95 ml) to isolate solid which is dried at 80-85° C. under atmosphericpressure till constant weight.

[0082] Part of the above-obtained solid was kept in oven to removeresidual organic solvents at 141-149° C. at 100-mbar pressure, for 3 andhalf hours, to afford desired Form X of Fexofenadine Hydrochloride M.R183-188° C.

Example 4 Preparation of Form X of Fexofenadine Hydrochloride

[0083] To pure Fexofenadine (50 g), toluene (500 ml) is added and themixture is refluxed azeotropically for about 3 hours. The reaction massis then cooled to room temperature followed by slow addition ofisopropanol hydrogen chloride, to pH 2. The reaction mass is thenstirred for about 15 and a half hours. The separated solid is filtered,washed with toluene (50 ml) and dried (Yield 43.3 g). Part of this solid(42 g) is suspended in ethyl acetate (420 ml) and refluxed for about 1hour (this operation was performed for removal of residual organicsolvents). The suspension is then cooled to room temperature and stirredfor 20 minutes. The reaction mass is filtered and washed with ethylacetate (42 ml). The desired Form X of Fexofenadine hydrochloride isdried at 90-96° C. to constant weight.

[0084] Yield 39 g: M.R 183-188° C.

Example 5

[0085] A suspension of pure Fexofenadine (prepared as per example 1; 100g) in toluene (1000 ml) is azeotropically refluxed for 3-4 hours. Thereaction mixture is then cooled to room temperature and stirred forabout 15-30 minutes. Subsequently, the reaction mixture is filtered andwashed with toluene (100 ml) and the Fexofenadine Form A obtained isdried below 100° C. to constant weight.

[0086] Yield 95 g

[0087] To a mixture of ethyl acetate and isopropanol (900:100 ml), isadded Fexofenadine Form A (100 g; prepared as per above procedure),followed by slow addition of isopropanol hydrogen chloride (prepared bypurging hydrogen chloride to isopropyl alcohol) to pH 2. The reactionmass is then filtered and to the filtrate is added several crystals ofForm X of4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzeneacetic acid hydrochloride. The reaction mixture is then stirred for 2-4hours. The solid obtained is filtered, washed with cyclohexane (200 ml)and dried below 100° C. to constant weight to obtain the desired Form Xof Fexofenadine Hydrochloride

[0088] Yield 100 g.

[0089] The aforementioned crystalline form X of Fexofenadinehydrochloride and Form A of Fexofenadine, in Examples 2-4 have beenexamined for their structural and analytical data viz., Powder X-RayDiffraction, Differential Scanning Calorimetry, and Infrared AbsorptionSpectroscopy.

[0090] The results obtained are discussed above and the respectivedrawings attached (FIGS. 1-6).

[0091] The X-Ray Diffraction Pattern set out herein were obtained usingRigaku D/Max-2200 X-Ray Powder Diffractometer having a Cu K-radiationsource of wavelength λ=1.54 A°. The samples were scanned between 3-45degrees 2θ.

[0092] The infrared absorption spectra were recorded in solid state asKBr dispersion on Perkin Ehner 1650 FT-IR spectrophotometer.

[0093] Differential Scanning Calorimetric analysis was performed on aShimadzu DSC-50. The samples were heated to 250° C. at a heating rate of5° C./min with a 30 ml/minute nitrogen purge.

1. A crystalline Form A of4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzeneacetic acid (Form A of Fexofenadine) which is characterized by thefollowing X-ray powder diffraction pattern (d values in A°): 23.11,11.50, 8.29, 7.03, 6.67, 6.16, 6.02, 5.75, 5.43, 5.33, 5.07, 4.69, 4.63,4.44, 4.20, 4.15, 4.07, 3.55, and 3.44:
 2. The crystalline Form A ofFexofenadine according to claim 1, characterized by the followinginfrared absorption peaks (in cm⁻¹) FT-IR (In KBr): 3421, 3058, 2936,2366, 2343, 1571, 1509, 1490, 1447, 1390, 1334, 1167, 1097, 1073, 1018,960, 916, 849, 745, 706, 666, 637, 617,
 541. 3. The crystalline Form Aof Fexofenadine according to claim 1, or 2, characterized by a meltendotherm with a peak temperature at about 227-231° C.
 4. A process forpreparing Form Aof4-[4-[4-hydroxydiphenylmethyl]-1-piperidin-yl]-α,α-dimethylbenzeneacetic acid (Form A of Fexofenadine) which comprises: a. recrystallizingcrude Fexofenadine in a (C₁-C₃) alkanol; b. azeotropically refluxingFexofenadine in a non polar organic solvent, an organic solvent or amixture thereof for 15 minutes to 6 hours; c. stirring the reactionmixture at ambient temperature for 30 minutes to 2 hours; and d.isolating the Form A of Fexofenadine.
 5. A pure Form A of4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1hydroxybutyl]-α,α-dimethylbenzeneacetic acid, according to any one of claims 1 to 3, wherein the purityof Form A is greater than 99.5%
 6. A crystalline Form X of4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzeneacetic acid hydrochloride (Form X of Fexofenadine Hydrochloride) offormula (1) which is characterized by the following X-ray powderdiffraction pattern (d values in A°): 16.05, 12.98, 8.29, 8.06, 6.25,5.97, 5.54, 5.41, 4.89, 4.70, 4.55, 4.37, 4.32, 4.15, 4.03, 3.80, 3.67,3.57, 3.42.
 7. The crystalline Form X of Fexofenadine Hydrochlorideaccording to claim 6, characterized by the following infrared absorptionpeaks (in cm⁻¹): FT-IR (In KBr): 3370, 2965, 2652, 1717, 1472, 1448,1250, 1158, 1100, 1068, 995, 962, 840, 747, 703, 638,
 560. 8. Thecrystalline Form X of Fexofenadine Hydrochloride according to claim 6 or7, characterized by the DSC thermogram exhibits a melt endotherm with apeak temperature of about at about 184-189° C.
 9. A process forpreparing Form X of4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzeneacetic acid hydrochloride (Form X of Fexofenadine Hydrochloride), whichcomprises: a. recrystallizing crude Fexofenadine in a (C₁-C₃) alkanol;b. azeotropically refluxing Fexofenadine in a non polar organic solventor organic solvent or a mixture thereof for 15 minutes to 6 hours; c.stirring the reaction mixture at ambient temperature for 30 min to 2hours; d. adjusting the pH, of the reaction mass to 1 to 3 with asolvent containing hydrogen chloride; e. stirring the reaction mass for30 minutes to 18 hours at ambient temperature; f. filtering the solidobtained followed by drying at 60-100° C.; g. suspending the solidobtained in step (f) in an alkyl acetate and heating the reactionmixture to reflux for 30 minutes to 6 hours; h. stirring the reactionmixture at ambient temperature for 20 minutes to 2 hours; and i.isolating the anhydrous crystalline Form X of4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzeneacetic acid hydrochloride.
 10. A process for preparing Form X of4-[4-[4-(hydroxydiphenyhnethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzeneacetic acid hydrochloride (Form X of Fexofenadine Hydrochloride), whichcomprises: a. recrystallizing crude Fexofenadine in a (C₁-C₃) alkanol;b. azeotropically refluxing Fexofenadine in a non polar organic solvent,organic solvent or a mixture thereof for 15 minutes to 6 hours; c.stirring the reaction mixture at ambient temperature for 30 min to 2hours; d. isolating Fexofenadine Form A; e. suspending isolated Form Aof Fexofenadine in a non polar organic solvent; f. adjusting the pH, ofthe reaction mass to 1 to 3 with a solvent containing hydrogen chloride;g. stirring the reaction mass for 30 minutes to 18 hours at ambienttemperature; h. filtering the solid obtained followed by drying at60-100° C. or by drying at 110-16 under reduced pressure; i. suspendingthe solid obtained in step (h) in an alkyl acetate and heating thereaction mixture to reflux for 30 minutes-6 hours; j. stirring thereaction mixture at ambient temperature for 20 minutes to 2 hours; andk. isolating the anhydrous crystalline Form X of4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzeneacetic acid hydrochloride, by conventional methods.
 11. A process forpreparing Form X of Fexofenadine Hydrochloride, which comprises: a)recrystallizing crude Fexofenadine in (C₁-C₃) alkanol; b) azeotropicallyrefluxing Fexofenadine in a non polar organic solvent for 3-4 hours; c)optionally isolating the Fexofenadine Form A obtained in step b) byconventional methods accompanied by drying at below 100° C.; d)suspending the Fexofenadine Form A obtained in step c) or adding to thereaction mixture of step b), a mixture of a nonpolar organic solvent oran organic solvent and isopropanol; e) adjusting the pH of the solutionof step e) to 1 to 3 with a solvent containing hydrogen chloride; f)filtering the solution obtained in step e) to remove particulate matter;g) seeding the solution of step f)with several crystals of crystallineForm X4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzeneacetic acid hydrochloride and stirring the reaction mass at ambienttemperature to separate the solid; i) filtering the solid obtained instep h) followed by washing with a nonpolar organic solvent, organicsolvent or hydrocarbon solvent; and j) drying the crystalline Form X4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzeneacetic acid hydrochloride.
 12. The process as claimed in any one ofclaims 4 or 9 to 11, wherein the non polar organic solvent is selectedfrom toluene or xylene.
 13. The process as claimed in any of claims 4 or9 to 12, wherein the (C₁-C₃) alkanol is methanol, ethanol or propanol.14. The process as claimed in any one of claims 4 or 9 to 13 wherein thenonpolar organic solvent is a (C₆-C₉) alkyl.
 15. The process as claimedin any one of claims 4 or 9 to 14, wherein the nonpolar organic solventis n-hexane, hexane, octane, nonane or cyclohexane.
 16. The process asclaimed in any one of claims 4 or 9 to 15, wherein the organic solventis selected from (C₁-C₄) alkyl acetate.
 17. The process according to anyone of claims 4 or 9 to 16, wherein the organic solvent is ethylacetate.
 18. The process as claimed in claim 9 step (d), claim 10 step(f) or claim 11 step (e) wherein the solvent containing hydrogenchloride is selected from methanol, ethanol, isopropanol or t-butanol.19. The process as claimed in claim 11 wherein the hydrocarbon solventis selected from hexane or cyclohexane.